Anthrax is considered a major bioterrorist threat because the spores of Bacillus anthracis are very hardy, easy to disperse, and potentially easy to obtain; anthrax vaccination is considered a critical component of the defense against this agent. Currently, there is one US-licensed anthrax vaccine and new vaccines are under development. The major antigen in this preparation is believed to be a protein known as protective antigen (PA) and research has indicated that antibodies to PA can protect against B. anthracis in animal models. Projects are being initiated to develop and standardize improved quality control tests for anthrax vaccines and to evaluate and standardize assays that can be used to evaluate the immune response in humans and relevant animal models. Quality control: Improved laboratory tests to assess the safety, purity, and potency of anthrax will enhance the control of the licensed vaccine and expedite licensure of new generation vaccines. Currently available methods assess the potency of anthrax vaccines by evaluating protection from a lethal challenge with virulent spores; the goals of project is to develop non-lethal animal methods that do not require viable bacteria and in vitro methods that eliminate the need for laboratory animals. Development and evaluation of a mouse model in which the immune response to specific components of the vaccine is measured is in progress. Mouse serum against anthrax vaccine has been obtained and is being used for the design of tests to detect antibodies to protective antigen (PA) on the basis of their binding and toxin-neutralizing properties. Serological assays: Development and standardization of appropriate immunologic assays is essential to the evaluation of experimental anthrax vaccines, since efficacy trials in humans will be impossible to conduct because of the low incidence of disease caused by these organisms and the toxicity of these agents that preclude human challenge studies. Thus information obtained from animal challenge studies will have to be translated into correlates of protection in humans. CBER has initiated a program to develop, standardize, and validate assays to assess the immune response to vaccination with the goal of defining appropriate immunological correlates of protection. An essential component of these activities will be the production and eventual distribution of appropriate reference reagents with the goal of international standardization of the assays. To date, we have conducted preliminary studies to develop an assay to measure anthrax toxin-neutralizing antibodies and initiated immunogenicity studies in mice.